WO2010114275A2 - Composition for inhibiting erythema caused by ultraviolet radiation containing a dipeptide as active ingredient - Google Patents

Composition for inhibiting erythema caused by ultraviolet radiation containing a dipeptide as active ingredient Download PDF

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Publication number
WO2010114275A2
WO2010114275A2 PCT/KR2010/001923 KR2010001923W WO2010114275A2 WO 2010114275 A2 WO2010114275 A2 WO 2010114275A2 KR 2010001923 W KR2010001923 W KR 2010001923W WO 2010114275 A2 WO2010114275 A2 WO 2010114275A2
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Prior art keywords
serine
alanine
tryptophan
valine
tyrosine
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PCT/KR2010/001923
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French (fr)
Korean (ko)
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WO2010114275A3 (en
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이현경
최혜령
강윤아
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주식회사 웰스킨
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Priority to JP2012503319A priority Critical patent/JP2012522043A/en
Priority to US13/258,935 priority patent/US20120070392A1/en
Publication of WO2010114275A2 publication Critical patent/WO2010114275A2/en
Publication of WO2010114275A3 publication Critical patent/WO2010114275A3/en

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A61K38/05—Dipeptides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/64—Proteins; Peptides; Derivatives or degradation products thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/16—Emollients or protectives, e.g. against radiation
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q17/00—Barrier preparations; Preparations brought into direct contact with the skin for affording protection against external influences, e.g. sunlight, X-rays or other harmful rays, corrosive materials, bacteria or insect stings
    • A61Q17/04—Topical preparations for affording protection against sunlight or other radiation; Topical sun tanning preparations
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A61Q19/004—Aftersun preparations

Definitions

  • the present invention relates to a composition for inhibiting erythema reaction caused by ultraviolet rays comprising a dipeptide as an active ingredient, more specifically, inhibiting the production of PGE 2 (prostaglandin E 2 ), which is a kind of inflammatory mediator whose synthesis is increased by ultraviolet rays.
  • PGE 2 prostaglandin E 2
  • the present invention relates to a technique capable of simultaneously controlling the erythema response and the inflammatory response caused by ultraviolet rays.
  • Skin reactions caused by ultraviolet rays include erythema reactions, sunburn, pigmentation, photoaging, and skin cancers.
  • the erythema reaction is immediate erythema and delayed erythema, which is thought to be because prostaglandins, histamine, serotonin, interleukin, etc. secreted from keratinocytes expand the blood vessels and increase the permeability of the vascular wall.
  • the present invention was developed with a focus on inhibiting the activity of prostaglandins in the above components.
  • Prostaglandins are found in almost every tissue and organ and are produced in cells with almost every nucleus except lymphocytes. Prostaglandins, made from fatty acids, act on a variety of cells, including platelets, endothelium, mast cells, and cyclooxygenase-1 (COX-1) or cyclooxygenase. It is biosynthesized by the -2 (cyclooxygenase-2, COX-2) pathway.
  • prostaglandins The basic skeleton of prostaglandins is prostanoic acid, which is named PGA, PGB, PGC, PGD, PGE, PGF, PGG, PGH, and PGI due to the difference in the ring structure in prostanoic acid. Therefore, the numbers 1, 2 and 3 are attached.
  • PGI 2 acts as an inhibitor of platelet aggregation
  • PGF 2 acts as a vasoconstrictor
  • PGE 2 acts as a vasodilator
  • bronchodilator gastric acid inhibitor
  • TXA 2 Acts to promote platelet aggregation.
  • PGE 2 in the prostaglandins has been reported to be involved in skin erythema and inflammatory response by ultraviolet light.
  • PGE and 2 can be seen that an important role in redness and inflammation caused by UV light, the production of PGE 2 If it can inhibit the erythema and inflammatory response due to ultraviolet light is thought to be able to control the present invention.
  • Korean Patent Publication No. 2007-0116134 discloses a personal care composition containing a dipeptide in which the C-terminal amino acid of the dipeptide-based molecule is threonine and a carrier or an injectable liquid, but for treating the keratinous tissue condition for the purpose. Not only is it limited to the use, but it can be seen that the type of dipeptide is also very limited.
  • Japanese Patent Publication No. 1997-124434 also discloses an external preparation for skin containing urea and a peptide, but it is a technique for external preparation for skin that suppresses the change of pH or the generation of ammonia odor and is excellent in moisturizing effect. It is not related to the technique related to erythema action by.
  • US Patent No. 3965260 discloses a technique for the treatment of rheumatism using a peptide.
  • the present invention relates to SI (serine-isoleucine), YK (tyrosine-lysine), VC (valine-cysteine), MD (methionine-aspartic acid), WF (tryptophan-phenylalanine), NR (asparagine-arginine), DP ( Aspartic acid-proline), YE (tyrosine-glutamic acid), RM (arginine-methionine), QT (glutamine-threonine), LH (leucine-histidine), SP (serine-proline), IT (isoleucine-threonine), FW (Phenylalanine-tryptophan), AP (alanine-proline), WP (tryptophan-proline), AN (alanine-asparagine), AE (alanine-glutamic acid), DT (aspartic acid-threonine), PT (proline-threonine) , WD (try
  • composition preferably further comprises a pharmaceutically acceptable carrier or excipient.
  • composition is preferably in the form of a skin, lotion, cream, foundation, essence, gel, pack, foam cleansing, cosmetics such as soap, or pharmaceutical ointment such as skin ointment.
  • UV-response composition comprising a specific dipeptide of the present invention inhibits the production of PGE 2 , inhibits the erythema and inflammation of the skin caused by ultraviolet light, can be used safely in the human body.
  • composition of the present invention may include a dipeptide by adjusting its content according to the purpose and method of use, and preferably comprises 0.001 to 30% by weight of the dipeptide in the total weight of the composition.
  • composition of the present invention may further comprise a pharmaceutically acceptable carrier or excipient.
  • Representative carriers or excipients include, for example, water, dextrins, or saline.
  • the UV reaction inhibiting composition of the present invention can also be used in the form of a cosmetic composition, detergent composition or pharmaceutical.
  • the formulation may be a softening lotion, a skin, a nourishing cream, a massage cream, an essence, a pack, a soap, a shampoo, a skin patch or a skin adhesive gel, and when used as a cleaning composition, it may be a face wash or a bath.
  • the UV-resisting composition may be prepared in the form of a warning agent, granules, lotions, powders, syrups, ointments, emulsions, suspensions, tablets or injections.
  • composition of the present invention is used to adjust the amount used according to the use and the state of the application site, for example, it is preferable to use once to three times a day at a concentration of 0.001 to 100 mg / mL per day.
  • Keratinocytes were seeded in 6 well plates for 100,000 cells in 2 mL KGM (keratinocyte growth medium) and incubated for 1 day, followed by 2 mL KBM (keratinocyte basal medium) containing 0.1% BSA (bovine serum albumin). Incubate for 24 hours more after replacing the medium. In the same medium, the final concentration of each dipeptide of Table 1 was added to 10 ug / mL and replaced with 2 mL of fresh medium prepared and pretreated for 24 hours. However, the positive control NS-398 (N194, Sigma, St. Louis, MO, USA) was pretreated to a concentration of 5 uM one hour before ultraviolet B irradiation.
  • KGM Keratinocyte growth medium
  • KBM Keratinocyte basal medium
  • BSA bovine serum albumin
  • the pretreated medium was transferred to a new 24-well plate, and 1 mL of DPBS (Dulbecco's phosphate buffered saline) was added to the cells.
  • the transferred medium was stored in a cell incubator while irradiated with ultraviolet light.
  • the cells were irradiated with ultraviolet B to 100 mJ / cm 2 .
  • the control group was covered with tinfoil. After UV irradiation, DPBS was removed and stored in the pretreatment medium.
  • the medium transferred to the tube was centrifuged at a speed of 12,000 to 15,000 rpm for 5 minutes using a microcentrifuge, and then the supernatant was stored in a freezer until the PGE 2 was measured in a new tube.
  • PGE 2 using the assay kit (KGE004, R & DSystems, Inc. , Minneapolis, MN, USA) method proposed by the manufacturer as to measure the PGE 2.
  • PGE 2 standard solutions were prepared to be 2500, 1250, 625, 312, 156, 78, 39 pg / mL.
  • the culture supernatants and the PGE 2 standard solutions prepared for each concentration were placed in 96 well plates provided by Kit at 100 uL. After the addition of primary antibodies PGE 2 in a state where the light blocking solution (Primary Antibody Solution) following the addition of 50uL PGE 2 conjugate (Conjugate) placed in a stirrer at room temperature, the reaction was carried out for 2 hours.
  • Primary Antibody Solution Primary Antibody Solution
  • the reaction solution was removed and the wells were washed five times by adding 400 uL of Wash Buffer. 200 uL of substrate solution was added to the wells and allowed to react for 20 to 30 minutes. After stopping the reaction by adding 50 uL of stop solution to the wells, the absorbance value was measured at 450 nm using an ELISA reader. PGE 2 concentration of each sample was calculated from the standard graph, and the MTT experiment result was corrected with absorbance values, and then the degree of inhibition of PGE 2 production was calculated. More than 10% was classified as an effective group, the effect of 0% or less is described as 0, the results are shown in Table 1 below.
  • A alanine
  • C cysteine
  • D aspartic acid
  • E glutamic acid
  • F phenylalanine
  • G glycine
  • H histidine
  • I isoleucine
  • K lysine
  • L leucine
  • M methionine
  • N asparagine
  • P proline
  • Q glutamine
  • R arginine
  • S serine
  • T threonine
  • V valine
  • W tryptophan
  • Y tyrosine.
  • composition comprising the dipeptide of Table 2 can be used as a final product of various forms.
  • any one or more of the dipeptides of Table 2 5.0% by weight of glycerin, 3.0% by weight of 1,3-butylene glycol, 1.0% by weight of Fiji-1500, 0.1% by weight of allantoin, 0.3% by weight of DL-panthenol %, EDTA-2NA 0.02 wt%, Benzophenone-9 0.04 wt%, Sodium hyaluronate 5.0 wt%, Ethanol 10.0 wt%, Octyldodeces-16 0.3 wt%, Polysorbate-20 0.3 wt% and trace amounts Softener longevity can be prepared by mixing preservatives, flavors, pigments and residual purified water. It is obvious that the content is exemplary and can be changed in various ranges.
  • 1.0% by weight of any one or more of the dipeptides of Table 2 2.0% by weight of glycerin, 2.0% by weight of 1,3-butylene glycol, 1.0% by weight of Fiji-1500, 0.2% by weight of allantoin, 0.2% by weight of DL-panthenol, 3.0 wt% sodium hyaluronate, 15.0 wt% ethanol, 0.2 wt% octyldodeces-16, 0.3 wt% polysorbate-20, 2.0 wt% witch hazel extract, and trace amounts of citric acid, preservatives, flavors, pigments and residuals Ointment may be prepared by mixing purified water. As the content is exemplary, it is obvious that the content can be changed within various ranges.
  • the dipeptide of Table 2 may be included to prepare a skin, lotion, cream, foundation, essence, cosmetics such as gels, packs, foam cleansing, soap, or a cosmetic ointment such as an external skin ointment.

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  • Animal Behavior & Ethology (AREA)
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Abstract

The present invention relates to a composition for inhibiting erythema caused by ultraviolet radiation, wherein said composition contains a specific dipeptide, selected from 400 dipeptides, as an active ingredient. The composition of the present invention inhibits the production of prostaglandin E2(PGE2), thereby inhibiting erythema caused by ultraviolet radiation.

Description

다이펩타이드를 유효성분으로 포함하는 자외선에 의한 홍반반응 억제조성물A composition for inhibiting erythema reaction caused by ultraviolet rays containing a dipeptide as an active ingredient
본 발명은 다이펩타이드를 유효성분으로 포함하는 자외선에 의한 홍반반응 억제조성물에 관한 것으로서, 더욱 상세하게는 자외선에 의해 합성이 증가하는 염증매개물질의 일종인 PGE2(prostaglandin E2)의 생산을 억제함으로써, 자외선에 의한 홍반반응과 염증반응을 동시에 조절할 수 있는 기술에 관한 것이다.The present invention relates to a composition for inhibiting erythema reaction caused by ultraviolet rays comprising a dipeptide as an active ingredient, more specifically, inhibiting the production of PGE 2 (prostaglandin E 2 ), which is a kind of inflammatory mediator whose synthesis is increased by ultraviolet rays. By doing so, the present invention relates to a technique capable of simultaneously controlling the erythema response and the inflammatory response caused by ultraviolet rays.
자외선에 의한 피부반응은 홍반반응과 일광화상, 색소침착, 광노화, 피부암발생 등이 있다. 상기 피부반응 중 홍반반응은 즉시홍반과 지연홍반이 있는데, 이는 각질형성세포에서 분비되는 프로스타글란딘, 히스타민, 세로토닌, 인터류킨 등이 혈관을 확장시키고 혈관벽의 투과성을 증가시키기 때문으로 생각된다. 본 발명은 상기 성분 중 프로스타글란딘의 활성 억제에 초점을 맞추어 개발되었다.Skin reactions caused by ultraviolet rays include erythema reactions, sunburn, pigmentation, photoaging, and skin cancers. Among the skin reactions, the erythema reaction is immediate erythema and delayed erythema, which is thought to be because prostaglandins, histamine, serotonin, interleukin, etc. secreted from keratinocytes expand the blood vessels and increase the permeability of the vascular wall. The present invention was developed with a focus on inhibiting the activity of prostaglandins in the above components.
프로스타글란딘은 거의 모든 조직과 장기에서 발견되며 림프구를 제외한 거의 모든 핵을 가진 세포에서 생산된다. 지방산으로부터 만들어지는 프로스타글란딘은 혈소판(platelet), 혈관내피(endothelium), 비만세포(mast cell) 등 다양한 세포에 작용하며, 사이클로옥시게나제-1(cyclooxygenase-1, COX-1) 또는 사이클로옥시게나제-2(cyclooxygenase-2,COX-2) 경로에 의해 생합성된다. Prostaglandins are found in almost every tissue and organ and are produced in cells with almost every nucleus except lymphocytes. Prostaglandins, made from fatty acids, act on a variety of cells, including platelets, endothelium, mast cells, and cyclooxygenase-1 (COX-1) or cyclooxygenase. It is biosynthesized by the -2 (cyclooxygenase-2, COX-2) pathway.
프로스타글란딘의 기본골격은 프로스탄산(prostanoic acid)이며, 프로스탄산 중의 환의 구조의 차이에 의해서 PGA, PGB, PGC, PGD, PGE, PGF, PGG, PGH, PGI로 명명하고, 측쇄의 이중결합의 수에 따라서 1, 2, 3의 숫자를 붙인다. 생리적으로 중요한 작용을 하는 프로스타글란딘의 예로, PGI2는 혈소판 응집억제 작용 등을 하며, PGF2는 혈관수축 작용 등을 하며, PGE2는 혈관확장, 기관지확장, 위산억제 등의 작용을 하며, TXA2는 혈소판 응집 촉진 등의 작용을 한다.The basic skeleton of prostaglandins is prostanoic acid, which is named PGA, PGB, PGC, PGD, PGE, PGF, PGG, PGH, and PGI due to the difference in the ring structure in prostanoic acid. Therefore, the numbers 1, 2 and 3 are attached. Examples of prostaglandins that have a physiologically important effect, PGI 2 acts as an inhibitor of platelet aggregation, PGF 2 acts as a vasoconstrictor, PGE 2 acts as a vasodilator, bronchodilator, gastric acid inhibitor, TXA 2 Acts to promote platelet aggregation.
특히, 상기 프로스타글란딘 중에서 PGE2는 자외선에 의한 피부홍반 및 염증 반응에 관여하는 것으로 보고되고 있다. PGE2의 수용체 가운데 EP2와 EP4가 결핍된 쥐에서 염증반응이 현저하게 감소한다는 사실을 보여주어, PGE2가 자외선에 의한 홍반과 염증반응에서 중요한 역할을 한다는 사실을 알 수 있으며, PGE2의 생산을 억제할 수 있다면 자외선에 의한 홍반 및 염증반응을 조절할 수 있을 것으로 생각되어 본 발명에 이르게 되었다.In particular, PGE 2 in the prostaglandins has been reported to be involved in skin erythema and inflammatory response by ultraviolet light. By showing that among the receptors of PGE 2 in the EP2 and the EP4-deficient mice inflammation is significantly reduced, PGE and 2 can be seen that an important role in redness and inflammation caused by UV light, the production of PGE 2 If it can inhibit the erythema and inflammatory response due to ultraviolet light is thought to be able to control the present invention.
현재, 펩타이드와 피부 염증과 관련된 특허를 살펴보면 다음과 같다.Currently, the patents related to peptides and skin inflammation are as follows.
대한민국특허공개번호 제2007-0116134호에서는, 다이펩티드계 분자의 C 말단 아미노산이 트레오닌인 다이펩타이드와 담체 또는 주사 가능한 액체를 함유하는 개인 케어 조성물을 공개하고 있으나, 그 목적에 있어서 각질 조직 상태를 처치하는 용도로 한정하고 있을 뿐만 아니라, 다이펩타이드의 종류도 매우 한정적임을 알 수 있다.Korean Patent Publication No. 2007-0116134 discloses a personal care composition containing a dipeptide in which the C-terminal amino acid of the dipeptide-based molecule is threonine and a carrier or an injectable liquid, but for treating the keratinous tissue condition for the purpose. Not only is it limited to the use, but it can be seen that the type of dipeptide is also very limited.
일본특허공개번호 제1997-124434호에서도 요소와 펩타이드를 함유한 피부외용제에 대하여 개시하고 있으나, pH 변화나 암모니아(ammonia) 냄새의 발생을 억제하고, 보습 효과에 우수한 피부 외용제에 대한 기술로서, 자외선에 의한 홍반 작용에 관한 기술과는 무관하다.Japanese Patent Publication No. 1997-124434 also discloses an external preparation for skin containing urea and a peptide, but it is a technique for external preparation for skin that suppresses the change of pH or the generation of ammonia odor and is excellent in moisturizing effect. It is not related to the technique related to erythema action by.
미국특허등록 제3965260호에서는 펩타이드를 이용하여 류마티즘 치료에 관한 기술을 공지하고 있다.US Patent No. 3965260 discloses a technique for the treatment of rheumatism using a peptide.
본 발명은 PGE2의 생산을 억제하여 자외선에 의한 피부반응, 특히, 홍반반응을 억제할 수 있는 특정한 다이펩타이드를 포함하는 조성물을 제공하는 데 목적이 있다.It is an object of the present invention to provide a composition comprising a specific dipeptide capable of inhibiting the production of PGE 2 to inhibit skin reactions caused by ultraviolet radiation, in particular, erythema reactions.
본 발명은 SI(세린-이소류신), YK(타이로신-라이신), VC(발린-시스테인), MD(메티오닌-아스파트산), WF(트립토판-페닐알라닌), NR(아스파라진-아르기닌), DP(아스파트산-프로린), YE(타이로신-글루탐산), RM(아르기닌-메티오닌), QT(글루타민-트레오닌), LH(류신-히스티딘), SP(세린-프로린), IT(이소류신-트레오닌), FW(페닐알라닌-트립토판), AP(알라닌-프로린), WP(트립토판-프로린), AN(알라닌-아스파라진), AE(알라닌-글루탐산), DT(아스파트산-트레오닌), PT(프로린-트레오닌), WD(트립토판-아스파트산), NA(아스파라진-알라닌), WY(트립토판-타이로신), AS(알라닌-세린), DG(아스파트산-글라이신), SY(세린-타이로신), NY(아스파라진-타이로신), LE(류신-글루탐산), VH(발린-히스티딘), TI(트레오닌-이소류신), LR(류신-아르기닌), FN(페닐알라닌-아스파라진), YR(타이로신-아르기닌), NE(아스파라진-글루탐산), SL(세린-류신), GL(글라이신-류신), MY(메티오닌-타이로신), AA(알라닌-알라닌), IQ(이소류신-글루타민), HH(히스티딘-히스티딘), NP(아스파라진-프로린), RP(아르기닌-프로린), SD(세린-아스파트산), AK(알라닌-라이신), TD(트레오닌-아스파트산), KY(라이신-타이로신), LF(류신-페닐알라닌), IK(이소류신-라이신), AF(알라닌-페닐알라닌), RS(아르기닌-세린), FK(페닐알라닌-라이신), ST(세린-트레오닌), EP(글루탐산-프로린), WL(트립토판-류신), NC(아스파라진-시스테인), RC(아르기닌-시스테인), SQ(세린-글루타민), WV(트립토판-발린), SM(세린-메티오닌), PA(프로린-알라닌), YA(타이로신-알라닌), HY(히스티딘-타이로신), YD(타이로신-아스파트산), RD(아르기닌-아스파트산), KD(라이신-아스파트산), DD(아스파트산-아스파트산), YI(타이로신-이소류신), AR(알라닌-아르기닌), AC(알라닌-시스테인), YQ(타이로신-글루타민), VF(발린-페닐알라닌), LC(류신-시스테인), KT(라이신-트레오닌), QW(글루타민-트립토판), RK(아르기닌-라이신), NL(아스파라진-류신), GQ(글라이신-글루타민), GI(글라이신-이소류신), HK(히스티딘-라이신), DH(아스파트산-히스티딘), VD(발린-아스파트산), VY(발린-타이로신), MT(메티오닌-트레오닌), QK(글루타민-라이신), TK(트레오닌-라이신), TV(트레오닌-발린), QQ(글루타민-글루타민), WC(트립토판-시스테인), YY(타이로신-타이로신), ET(글루탐산-트레오닌), QF(글루타민-페닐알라닌), RN(아르기닌-아스파라진), TR(트레오닌-아르기닌), AQ(알라닌-글루타민), GD(글라이신-아스파트산), WA(트립토판-알라닌), IH(이소류신-히스티딘), WW(트립토판-트립토판), QN(글루타민-아스파라진), VI(발린-이소류신), AD(알라닌-아스파트산), VN(발린-아스파라진), CW(시스테인-트립토판), EI(글루탐산-이소류신), SN(세린-아스파라진), WN(트립토판-아스파라진), TG(트레오닌-글라이신), SA(세린-알라닌), GA(글라이신-알라닌), PW(프로린-트립토판), PQ(프로린-글루타민), IG(이소류신-글라이신), SH(세린-히스티딘), VR(발린-아르기닌), KM(라이신-메티오닌), VK(발린-라이신), GF(글라이신-페닐알라닌), NV(아스파라진-발린), RG(아르기닌-글라이신), HW(히스티딘-트립토판), VQ(발린-글루타민), CM(시스테인-메티오닌), KC(라이신-시스테인), WQ(트립토판-글루타민), PD(프로린-아스파트산), NQ(아스파라진-글루타민), AY(알라닌-타이로신), GS(글라이신-세린), TW(트레오닌-트립토판), EF(글루탐산-페닐알라닌), EG(글루탐산-글라이신), IV(이소류신-발린), QY(글루타민-타이로신), HL(히스티딘-류신), SK(세린-라이신), ID(이소류신-아스파트산), TS(트레오닌-세린), GW(글라이신-트립토판), PI(프로린-이소류신), NH(아스파라진-히스티딘), PY(프로린-타이로신), TP(트레오닌-프로린), ED(글루탐산-아스파트산), DV(아스파트산-발린), DA(아스파트산-알라닌), NT(아스파라진-트레오닌), DQ(아스파트산-글루타민), PF(프로린-페닐알라닌), SV(세린-발린), DS(아스파트산-세린), GY(글라이신-타이로신), WR(트립토판-아르기닌), NN(아스파라진-아스파라진), FA(페닐알라닌-알라닌), TQ(트레오닌-글루타민), IS(이소류신-세린), VE(발린-글루탐산), FR(페닐알라닌-아르기닌), QR(글루타민-아르기닌), RL(아르기닌-류신), TM(트레오닌-메티오닌), CN(시스테인-아스파라진), FL(페닐알라닌-류신), TE(트레오닌-글루탐산), DI(아스파트산-이소류신), RW(아르기닌-트립토판), RT(아르기닌-트레오닌), MQ(메티오닌-글루타민), VP(발린-프로린), WK(트립토판-라이신), QH(글루타민-히스티딘), SE(세린-글루탐산), AG(알라닌-글라이신), HS(히스티딘-세린), HP(히스티딘-프로린), RE(아르기닌-글루탐산), QS(글루타민-세린), SG(세린-글라이신), AL(알라닌-류신), VA(발린-알라닌), YL(타이로신-류신), YT(타이로신-트레오닌), SR(세린-아르기닌), WS(트립토판-세린), RY(아르기닌-타이로신), FI(페닐알라닌-이소류신), VG(발린-글라이신), LV(류신-발린), WM(트립토판-메티오닌), DW(아스파트산-트립토판), DC(아스파트산-시스테인), FG(페닐알라닌-글라이신), HF(히스티딘-페닐알라닌), PG(프로린-글라이신), CE(시스테인-글루탐산), VV(발린-발린), DN(아스파트산-아스파라진), FH(페닐알라닌-히스티딘), GH(글라이신-히스티딘), MW(메티오닌-트립토판), IP(이소류신-프로린), AI(알라닌-이소류신), ES(글루탐산-세린), EA(글루탐산-알라닌), QV(글루타민-발린), MR(메티오닌-아르기닌), VL(발린-류신), PK(프로린-라이신), DM(아스파트산-메티오닌), GG(글라이신-글라이신), YF(타이로신-페닐알라닌), EE(글루탐산-글루탐산), TF(트레오닌-페닐알라닌), ER(글루탐산-아르기닌), CS(시스테인-세린), IA(이소류신-알라닌), YM(타이로신-메티오닌), IM(이소류신-메티오닌), EV(글루탐산-발린), SS(세린-세린), AH(알라닌-히스티딘), EH(글루탐산-히스티딘), NF(아스파라진-페닐알라닌), EM(글루탐산-메티오닌), HA(히스티딘-알라닌), RR(아르기닌-아르기닌), IY(이소류신-타이로신), SC(세린-시스테인), GK(글라이신-라이신), PS(프로린-세린), EY(글루탐산-타이로신), LK(류신-라이신), CQ(시스테인-글루타민), KV(라이신-발린), WE(트립토판-글루탐산), HG(히스티딘-글라이신), EK(글루탐산-라이신), FF(페닐알라닌-페닐알라닌), FM(페닐알라닌-메티오닌), DK(아스파트산-라이신), LT(류신-트레오닌), FD(페닐알라닌-아스파트산), DF(아스파트산-페닐알라닌), FY(페닐알라닌-타이로신), QD(글루타민-아스파트산), LN(류신-아스파라진), KW(라이신-트립토판), NS(아스파라진-세린), PH(프로린-히스티딘), WG(트립토판-글라이신), EL(글루탐산-류신), EQ(글루탐산-글루타민), LA(류신-알라닌), NG(아스파라진-글라이신), NM(아스파라진-메티오닌), WH(트립토판-히스티딘), DE(아스파트산-글루탐산), DL(아스파트산-류신), AV(알라닌-발린), PN(프로린-아스파라진) 및 PR(프로린-아르기닌) 중에서 선택되는 하나 이상의 다이펩타이드를 유효성분으로 포함하는 것을 특징으로 하는 자외선에 의한 홍반반응 억제 조성물을 제공한다.The present invention relates to SI (serine-isoleucine), YK (tyrosine-lysine), VC (valine-cysteine), MD (methionine-aspartic acid), WF (tryptophan-phenylalanine), NR (asparagine-arginine), DP ( Aspartic acid-proline), YE (tyrosine-glutamic acid), RM (arginine-methionine), QT (glutamine-threonine), LH (leucine-histidine), SP (serine-proline), IT (isoleucine-threonine), FW (Phenylalanine-tryptophan), AP (alanine-proline), WP (tryptophan-proline), AN (alanine-asparagine), AE (alanine-glutamic acid), DT (aspartic acid-threonine), PT (proline-threonine) , WD (tryptophan-aspartic acid), NA (asparagine-alanine), WY (tryptophan-tyrosine), AS (alanine-serine), DG (aspartic acid-glycine), SY (serine-tyrosine), NY ( Asparagine-tyrosine), LE (leucine-glutamic acid), VH (valine-histidine), TI (threonine-isoleucine), LR (leucine-arginine), FN (phenylalanine-asparagine), YR (tyrosine-arginine), NE (As Razine-glutamic acid), SL (serine-leucine), GL (glycine-leucine), MY (methionine-tyrosine), AA (alanine-alanine), IQ (isoleucine-glutamine), HH (histidine-histidine), NP (aspa Razine-proline), RP (arginine-proline), SD (serine-aspartic acid), AK (alanine-lysine), TD (threonine-aspartic acid), KY (lysine-tyrosine), LF (leucine-phenylalanine) , IK (isoleucine-lysine), AF (alanine-phenylalanine), RS (arginine-serine), FK (phenylalanine-lysine), ST (serine-threonine), EP (glutamic acid-proline), WL (tryptophan-leucine), NC (asparagine-cysteine), RC (arginine-cysteine), SQ (serine-glutamine), WV (tryptophan-valine), SM (serine-methionine), PA (proline-alanine), YA (tyrosine-alanine), HY (histidine-tyrosine), YD (tyrosine-aspartic acid), RD (arginine-aspartic acid), KD (lysine-aspartic acid), DD (aspartic acid-aspartic acid), YI (tyrosine-isoleucine ), AR (alanine-arginine), A C (alanine-cysteine), YQ (tyrosine-glutamine), VF (valine-phenylalanine), LC (leucine-cysteine), KT (lysine-threonine), QW (glutamine-tryptophan), RK (arginine-lysine), NL (Asparagine-leucine), GQ (glycine-glutamine), GI (glycine-isoleucine), HK (histidine-lysine), DH (aspartic acid-histidine), VD (valine-aspartic acid), VY (valine- Tyrosine), MT (methionine-threonine), QK (glutamine-lysine), TK (threonine-lysine), TV (threonine-valine), QQ (glutamine-glutamine), WC (tryptophan-cysteine), YY (tyrosine-tyrosine) ), ET (glutamic acid-threonine), QF (glutamine-phenylalanine), RN (arginine-asparagine), TR (threonine-arginine), AQ (alanine-glutamine), GD (glycine-aspartic acid), WA (tryptophan) -Alanine), IH (isoleucine-histidine), WW (tryptophan-tryptophan), QN (glutamine-asparagine), VI (valine-isoleucine), AD (alanine-aspartic acid), VN (valine-asparta) Gene), CW (cysteine-tryptophan), EI (glutamic acid-isoleucine), SN (serine-asparagine), WN (tryptophan-asparagine), TG (threonine-glycine), SA (serine-alanine), GA (glycine) Alanine), PW (proline-tryptophan), PQ (proline-glutamine), IG (isoleucine-glycine), SH (serine-histidine), VR (valine-arginine), KM (lysine-methionine), VK (valine- Lysine), GF (glycine-phenylalanine), NV (asparagine-valine), RG (arginine-glycine), HW (histidine-tryptophan), VQ (valine-glutamine), CM (cysteine-methionine), KC (lysine- Cysteine), WQ (tryptophan-glutamine), PD (proline-aspartic acid), NQ (asparagine-glutamine), AY (alanine-tyrosine), GS (glycine-serine), TW (threonine-tryptophan), EF ( Glutamic acid-phenylalanine), EG (glutamic acid-glycine), IV (isoleucine-valine), QY (glutamine-tyrosine), HL (histidine-leucine), SK (serine-lysine), ID (isoleucine-aspartic acid), TS (Tre Nin-serine), GW (glycine-tryptophan), PI (proline-isoleucine), NH (asparagine-histidine), PY (proline-tyrosine), TP (threonine-proline), ED (glutamic acid-aspartic acid), DV (aspartic acid-valine), DA (aspartic acid-alanine), NT (asparagine-threonine), DQ (aspartic acid-glutamine), PF (proline-phenylalanine), SV (serine-valine), DS (Aspartic acid-serine), GY (glycine-tyrosine), WR (tryptophan-arginine), NN (asparagine-asparagine), FA (phenylalanine-alanine), TQ (threonine-glutamine), IS (isoleucine-serine ), VE (valine-glutamic acid), FR (phenylalanine-arginine), QR (glutamine-arginine), RL (arginine-leucine), TM (threonine-methionine), CN (cysteine-asparagine), FL (phenylalanine-leucine ), TE (threonine-glutamic acid), DI (aspartic acid-isoleucine), RW (arginine-tryptophan), RT (arginine-threonine), MQ (methionine-glutamine), VP (valine-proline), WK (tryptophan- Rai ), QH (glutamine-histidine), SE (serine-glutamic acid), AG (alanine-glycine), HS (histidine-serine), HP (histidine-proline), RE (arginine-glutamic acid), QS (glutamine-serine) , SG (serine-glycine), AL (alanine-leucine), VA (valine-alanine), YL (tyrosine-leucine), YT (tyrosine-threonine), SR (serine-arginine), WS (tryptophan-serine), RY (arginine-tyrosine), FI (phenylalanine-isoleucine), VG (valine-glycine), LV (leucine-valine), WM (tryptophan-methionine), DW (aspartic acid-tryptophan), DC (aspartic acid- Cysteine), FG (phenylalanine-glycine), HF (histidine-phenylalanine), PG (proline-glycine), CE (cysteine-glutamic acid), VV (valine-valine), DN (aspartic acid-asparagine), FH ( Phenylalanine-histidine), GH (glycine-histidine), MW (methionine-tryptophan), IP (isoleucine-proline), AI (alanine-isoleucine), ES (glutamic acid-serine), EA (glutamic acid-alanine), QV (glutamic acid-alanine) Valine), MR (meth) Thionine-arginine), VL (valine-leucine), PK (proline-lysine), DM (aspartic acid-methionine), GG (glycine-glycine), YF (tyrosine-phenylalanine), EE (glutamic acid-glutamic acid), TF (threonine-phenylalanine), ER (glutamic acid-arginine), CS (cysteine-serine), IA (isoleucine-alanine), YM (tyrosine-methionine), IM (isoleucine-methionine), EV (glutamic acid-valine), SS (Serine-serine), AH (alanine-histidine), EH (glutamic acid-histidine), NF (asparagine-phenylalanine), EM (glutamic acid-methionine), HA (histidine-alanine), RR (arginine-arginine), IY (Isoleucine-tyrosine), SC (serine-cysteine), GK (glycine-lysine), PS (proline-serine), EY (glutamic acid-tyrosine), LK (leucine-lysine), CQ (cysteine-glutamine), KV ( Lysine-valine), WE (tryptophan-glutamic acid), HG (histidine-glycine), EK (glutamic acid-lysine), FF (phenylalanine-phenylalanine), FM (phenylalanine-methionine), DK (aspartic acid) -Lysine), LT (leucine-threonine), FD (phenylalanine-aspartic acid), DF (aspartic acid-phenylalanine), FY (phenylalanine-tyrosine), QD (glutamine-aspartic acid), LN (leucine-aspartic acid) Razine), KW (lysine-tryptophan), NS (asparagine-serine), PH (proline-histidine), WG (tryptophan-glycine), EL (glutamic acid-leucine), EQ (glutamic acid-glutamine), LA (leucine- Alanine), NG (asparagine-glycine), NM (asparagine-methionine), WH (tryptophan-histidine), DE (aspartic acid-glutamic acid), DL (aspartic acid-leucine), AV (alanine-valine) It provides a composition for inhibiting erythema by ultraviolet rays, comprising at least one dipeptide selected from PN (proline-asparagine) and PR (proline-arginine) as an active ingredient.
특히, 상기 조성물 총중량 중 상기 다이펩타이드를 0.001 ~ 30 중량% 함유하는 것이 바람직하다.In particular, it is preferable to contain 0.001 to 30% by weight of the dipeptide in the total weight of the composition.
특히, 상기 조성물은 약학적으로 허용 가능한 담체 또는 부형제를 더 포함하는 것이 바람직하다.In particular, the composition preferably further comprises a pharmaceutically acceptable carrier or excipient.
특히, 상기 조성물은 스킨, 로션, 크림, 파운데이션, 에센스, 젤, 팩, 폼 클렌징, 비누와 같은 화장료, 또는 피부외용 연고와 같은 약품 연고 형태인 것이 바람직하다.In particular, the composition is preferably in the form of a skin, lotion, cream, foundation, essence, gel, pack, foam cleansing, cosmetics such as soap, or pharmaceutical ointment such as skin ointment.
본 발명의 특정한 다이펩타이드를 포함하는 자외선 반응 억제 조성물은 PGE2의 생산을 억제하여, 자외선으로 의한 피부의 홍반과 염증발생을 억제하고, 인체에 안전하게 사용될 수 있다.UV-response composition comprising a specific dipeptide of the present invention inhibits the production of PGE 2 , inhibits the erythema and inflammation of the skin caused by ultraviolet light, can be used safely in the human body.
일반적으로 펩타이드를 합성하는 데에 비용이 많이 들고 길이가 긴 경우 흡수가 잘 되지 않는 문제가 있다. 본 발명에서는 합성의 비용을 경감시키고 흡수의 문제도 감소시킬 수 있는 다이펩타이드가 자외선에 의해 생성되는 PGE2를 억제하여 자외선 반응조절효과가 있는지를 알아보고자 하였다. 이를 위하여 두개의 아미노산으로 구성된 다이펩타이드 라이브러리 400개를 구성하고, 배양한 각질형성세포에 자외선을 조사하여 PGE2의 생성억제효과를 실험하였다.In general, there is a problem in that the absorption is not good if the cost is long and long to synthesize the peptide. In the present invention, it was intended to determine whether the dipeptide, which can reduce the cost of synthesis and reduce the problem of absorption, inhibits PGE 2 produced by ultraviolet light and has an ultraviolet reaction control effect. To this end, 400 dipeptide libraries consisting of two amino acids were constructed, and cultured keratinocytes were irradiated with UV light to investigate the effect of inhibiting the production of PGE 2 .
후술할 내용과 같이 400개의 모든 다이펩타이드에서 자외선에 의한 홍반 및 염증반응을 제어할 수 있는 것은 아니며, 특정한 다이펩타이드만이 효과를 발휘한다는 것을 알 수 있었으며, 그 결과는 하기의 표 2와 같다.As described below, not all 400 dipeptides can control the erythema and inflammatory reactions caused by ultraviolet light, and it can be seen that only a specific dipeptide exerts an effect, and the results are shown in Table 2 below.
본 발명의 조성물은 다이펩타이드를 사용목적 및 사용방법에 따라 그 함량을 조절하여 포함할 수 있으며, 조성물 총중량 중 0.001 ~ 30 중량%의 다이펩타이드를 포함하는 것이 바람직하다.The composition of the present invention may include a dipeptide by adjusting its content according to the purpose and method of use, and preferably comprises 0.001 to 30% by weight of the dipeptide in the total weight of the composition.
또한, 본 발명의 조성물은 약학적으로 허용 가능한 담체 또는 부형제를 더 포함할 수 있다. 대표적인 담체 또는 부형제로는 물, 덱스트린 또는 생리식염수를 예로 들 수 있다.In addition, the composition of the present invention may further comprise a pharmaceutically acceptable carrier or excipient. Representative carriers or excipients include, for example, water, dextrins, or saline.
또한, 본 발명의 자외선반응 억제조성물은 또한 화장료 조성물, 세정제 조성물 또는 약제 형태로 사용될 수 있다. 화장료 조성물로 사용될 경우, 제형은 유연화장수, 스킨, 영양크림, 마사지크림, 에센스, 팩, 비누, 샴푸, 피부접착용 패취 또는 피부접착용 겔일 수 있으며, 세정제 조성물로 사용될 경우, 세안제 또는 목욕제일 수 있다. 약제로 사용될 경우, 자외선반응 억제 조성물은 경고제, 과립제, 로션제, 산제, 시럽제, 연고제, 에멀전제, 현탁제, 정제 또는 주사제 등의 제형으로 제조하여 사용할 수 있다.In addition, the UV reaction inhibiting composition of the present invention can also be used in the form of a cosmetic composition, detergent composition or pharmaceutical. When used as a cosmetic composition, the formulation may be a softening lotion, a skin, a nourishing cream, a massage cream, an essence, a pack, a soap, a shampoo, a skin patch or a skin adhesive gel, and when used as a cleaning composition, it may be a face wash or a bath. have. When used as a medicament, the UV-resisting composition may be prepared in the form of a warning agent, granules, lotions, powders, syrups, ointments, emulsions, suspensions, tablets or injections.
본 발명의 조성물은 사용 용도 및 적용 부위의 상태에 따라 사용량을 조절하여 사용하며, 일예로 1 일 0.001 내지 100 mg/mL의 농도로 하루 1회 내지 3 회 사용하는 것이 바람직하다.The composition of the present invention is used to adjust the amount used according to the use and the state of the application site, for example, it is preferable to use once to three times a day at a concentration of 0.001 to 100 mg / mL per day.
이하 본 발명의 실시예를 기재한다. 하기 실시예는 본 발명을 예시하기 위한 것일 뿐 본 발명의 보호범위가 하기 실시예에 한정되는 것은 아니다. Hereinafter, examples of the present invention will be described. The following examples are only for illustrating the present invention, but the protection scope of the present invention is not limited to the following examples.
자외선 B 조사에 의한 By ultraviolet B irradiation PGEPGE 22 생성 유도Generate induction
각질형성세포를 KGM(keratinocyte growth medium) 2 mL 안에 100,000개가 되도록 6 웰플레이트(well plate)에 뿌려서 하루 동안 배양한 후, 0.1% BSA(bovine serum albumin)가 포함된 KBM(keratinocyte basal medium) 2 mL로 배지를 교체한 후 24시간 더 배양하였다. 같은 배지에 표 1의 각 다이펩타이드의 최종농도가 10 ug/mL 되도록 첨가하여 준비한 새 배지 2 mL로 교체한 후 24시간 동안 전처리하였다. 단, 양성대조군인 NS-398 (N194, Sigma, St. Louis, MO, USA)은 자외선 B를 조사하기 한 시간 전에 5 uM 농도로 전처리하였다. 전처리 한 배지를 새 24 웰플레이트에 옮겨 담고 세포에 DPBS(Dulbecco's phosphate buffered saline) 1 mL씩 넣었다. 옮겨 담은 배지는 자외선을 조사하는 동안 세포배양기에 넣어 보관하였다. PGE2생산을 유도하기 위하여 자외선 B를 100 mJ/cm2 되도록 세포에 조사하였다. 이 때 대조군은 은박지로 가려두었다. 자외선 조사 후 DPBS를 제거하고 보관해 둔 전처리 배지를 다시 넣어 주었다. 24시간 더 배양한 후 배지 2 mL 중 1 mL을 마이크로원심분리튜브(microcentrifuge tube)에 옮겨 담고 약 1 mL의 배지가 남은 세포에 MTT(3-(4,5-dimetylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide) 용액 100 uL를 첨가하여 3~4시간 세포배양기에서 반응시켰다. MTT 용액이 포함된 배지를 제거하고, DMSO(Dimethyl sulfoxide) 1 mL을 넣어서 포르마잔(formazan)을 충분히 용해시킨 후, 200 uL를 96 웰플레이트에 취하여 ELISA(enzyme-linked immunosorbent assay) 리더를 이용하여 540 nm 파장에서 흡광도를 측정하였다. 한편 튜브에 옮겨 담은 배지는 미량원심분리기를 이용하여 냉장 조건에서 12,000~15,000 rpm 속도로 5분간 원심분리 한 후, 상등액을 새 튜브에 담아서 PGE2를 측정할 때까지 냉동고에 보관하였다. Keratinocytes were seeded in 6 well plates for 100,000 cells in 2 mL KGM (keratinocyte growth medium) and incubated for 1 day, followed by 2 mL KBM (keratinocyte basal medium) containing 0.1% BSA (bovine serum albumin). Incubate for 24 hours more after replacing the medium. In the same medium, the final concentration of each dipeptide of Table 1 was added to 10 ug / mL and replaced with 2 mL of fresh medium prepared and pretreated for 24 hours. However, the positive control NS-398 (N194, Sigma, St. Louis, MO, USA) was pretreated to a concentration of 5 uM one hour before ultraviolet B irradiation. The pretreated medium was transferred to a new 24-well plate, and 1 mL of DPBS (Dulbecco's phosphate buffered saline) was added to the cells. The transferred medium was stored in a cell incubator while irradiated with ultraviolet light. In order to induce PGE 2 production, the cells were irradiated with ultraviolet B to 100 mJ / cm 2 . At this time, the control group was covered with tinfoil. After UV irradiation, DPBS was removed and stored in the pretreatment medium. After 24 hours of incubation, 1 mL of 2 mL of medium was transferred to a microcentrifuge tube, and MTT (3- (4,5-dimetylthiazol-2-yl) -2 was added to the remaining cells of about 1 mL of medium. 100 uL of, 5-diphenyltetrazoliumbromide) solution was added and reacted in the cell incubator for 3-4 hours. Remove the medium containing the MTT solution, add 1 mL of dimethyl sulfoxide (DMSO) to sufficiently dissolve formazan, and then take 200 uL into 96 well plates and use an enzyme-linked immunosorbent assay (ELISA) reader. Absorbance was measured at a wavelength of 540 nm. Meanwhile, the medium transferred to the tube was centrifuged at a speed of 12,000 to 15,000 rpm for 5 minutes using a microcentrifuge, and then the supernatant was stored in a freezer until the PGE 2 was measured in a new tube.
PGEPGE 22 측정Measure
PGE2 분석키트 (KGE004, R&DSystems, Inc., Minneapolis, MN, USA)를 이용하여 제조사에서 제시한 방법대로 PGE2를 측정하였다. PGE2 표준용액을 2500, 1250, 625, 312, 156, 78, 39 pg/mL 농도가 되도록 준비하였다. 실험하여 보관해 둔 배지 상등액들과 농도별로 준비한 PGE2 표준용액들을 100 uL씩 Kit에서 제공한 96 웰플레이트에 넣었다. 빛을 차단한 상태에서 PGE2 일차항체용액(Primary Antibody Solution) 50uL를 첨가한 다음 PGE2 컨쥬게이트(Conjugate)를 첨가한 후 실온에서 교반기에 놓고 2시간 동안 반응시켰다. 반응액을 제거하고 워시버퍼(Wash Buffer) 400 uL를 첨가하여 웰(well)을 5회 세척하였다. 기질용액(Substrate Solution) 200 uL씩 웰에 첨가한 후 20~30분간 반응시켰다. 종결용액(Stop Solution) 50 uL씩 웰에 첨가하여 반응을 중지시킨 후 ELISA 리더를 이용하여 450 nm 파장에서 흡광도 값을 측정하였다. 스탠다드 그래프로부터 각 샘플의 PGE2농도를 산출하여 MTT 실험 결과 흡광도 값으로 보정한 후 PGE2생성 억제 정도를 계산하였다. 10% 이상을 효과 있는 군으로 분류하였으며, 0% 이하의 효과는 0으로 기재하였으며, 그 결과는 하기의 표1과 같다. PGE 2 using the assay kit (KGE004, R & DSystems, Inc. , Minneapolis, MN, USA) method proposed by the manufacturer as to measure the PGE 2. PGE 2 standard solutions were prepared to be 2500, 1250, 625, 312, 156, 78, 39 pg / mL. The culture supernatants and the PGE 2 standard solutions prepared for each concentration were placed in 96 well plates provided by Kit at 100 uL. After the addition of primary antibodies PGE 2 in a state where the light blocking solution (Primary Antibody Solution) following the addition of 50uL PGE 2 conjugate (Conjugate) placed in a stirrer at room temperature, the reaction was carried out for 2 hours. The reaction solution was removed and the wells were washed five times by adding 400 uL of Wash Buffer. 200 uL of substrate solution was added to the wells and allowed to react for 20 to 30 minutes. After stopping the reaction by adding 50 uL of stop solution to the wells, the absorbance value was measured at 450 nm using an ELISA reader. PGE 2 concentration of each sample was calculated from the standard graph, and the MTT experiment result was corrected with absorbance values, and then the degree of inhibition of PGE 2 production was calculated. More than 10% was classified as an effective group, the effect of 0% or less is described as 0, the results are shown in Table 1 below.
표1 : PGE2 억제율 실험결과Table 1: PGE 2 Inhibition Rate Experiment Results
[규칙 제91조에 의한 정정 08.06.2010]　
Figure PCTKR2010001923-appb-I000001
[Revision under Rule 91 08.06.2010]
Figure PCTKR2010001923-appb-I000001
(앞 페이지의 표1 이어짐)(Continued Table 1 on previous page)
[규칙 제91조에 의한 정정 08.06.2010]　
Figure PCTKR2010001923-appb-I000002
[Revision under Rule 91 08.06.2010]
Figure PCTKR2010001923-appb-I000002
상기 표1에서 , A=알라닌, C=시스테인, D=아스파트산, E = 글루탐산, F=페닐알라닌, G=글라이신, H=히스티딘, I=이소류신, K=라이신, L=류신, M=메티오닌, N=아스파라진, P=프로린, Q=글루타민, R=아르기닌, S=세린, T=트레오닌, V=발린, W=트립토판, Y=타이로신을 의미한다.In Table 1, A = alanine, C = cysteine, D = aspartic acid, E = glutamic acid, F = phenylalanine, G = glycine, H = histidine, I = isoleucine, K = lysine, L = leucine, M = methionine , N = asparagine, P = proline, Q = glutamine, R = arginine, S = serine, T = threonine, V = valine, W = tryptophan, Y = tyrosine.
20개의 아미노산으로부터 합성된 다이펩타이드 400개에 대하여 실험한 결과 표1과 같이 일정 다이펩타이드에서만 PGE2의 억제효과가 있음을 확인하였다. 상기 표1 중에서 PGE2의 억제효과가 있는 다이펩타이드만을 정리한 것이 하기의 표 2이다.As a result of experimenting with 400 dipeptides synthesized from 20 amino acids, it was confirmed that PGE 2 had an inhibitory effect only in certain dipeptides as shown in Table 1. Table 2 summarizes only the dipeptides having the inhibitory effect of PGE 2 in Table 1 below.
표 2 : PGE2 억제효과가 있는 다이펩타이드 Table 2: Dipeptides with PGE 2 Inhibitory Effect
[규칙 제91조에 의한 정정 08.06.2010]　
Figure PCTKR2010001923-appb-I000003
[Revision under Rule 91 08.06.2010]
Figure PCTKR2010001923-appb-I000003
또한, 상기 표2의 다이펩타이드를 포함하는 조성물은 다양한 형태의 최종 제품으로 사용될 수 있다.In addition, the composition comprising the dipeptide of Table 2 can be used as a final product of various forms.
예를 들어, 표2의 어느 하나 이상의 다이펩타이드 1.0 중량%, 글리세린 5.0 중량%, 1,3-부틸렌글리콜 3.0 중량%, 피이지-1500 1.0 중량%, 알란토인 0.1 중량%, DL-판테놀 0.3 중량%, EDTA-2NA 0.02 중량%, 벤조페논-9 0.04 중량%, 소듐히아루로네이트 5.0 중량%, 에탄올 10.0 중량%, 옥틸도데세스-16 0.3중량%, 폴리솔베이트-20 0.3중량% 및 미량의 방부제, 향, 색소와 잔량의 정제수를 혼합하여 유연화장수를 제조할 수 있다. 상기 함량은 예시적인 것으로서 다양한 범위 내에서 함량의 변화가 가능함은 당연하다.For example, 1.0% by weight of any one or more of the dipeptides of Table 2, 5.0% by weight of glycerin, 3.0% by weight of 1,3-butylene glycol, 1.0% by weight of Fiji-1500, 0.1% by weight of allantoin, 0.3% by weight of DL-panthenol %, EDTA-2NA 0.02 wt%, Benzophenone-9 0.04 wt%, Sodium hyaluronate 5.0 wt%, Ethanol 10.0 wt%, Octyldodeces-16 0.3 wt%, Polysorbate-20 0.3 wt% and trace amounts Softener longevity can be prepared by mixing preservatives, flavors, pigments and residual purified water. It is obvious that the content is exemplary and can be changed in various ranges.
또한, 표2의 어느 하나 이상의 다이펩타이드 1.0 중량%, 글리세린 2.0 중량%, 1,3-부틸렌글리콜 2.0 중량%, 피이지-1500 1.0 중량%, 알란토인 0.2 중량%, DL-판테놀 0.2 중량%, 소듐히아루로네이트 3.0 중량%, 에탄올 15.0 중량%, 옥틸도데세스-16 0.2 중량%, 폴리솔베이트-20 0.3 중량%, 위치하젤추출물 2.0 중량%, 및 미량의 구연산, 방부제, 향, 색소와 잔량의 정제수를 혼합하여 연고를 제조할 수 있다. 상기 함량은 예시적인 것으로서, 다양한 범위 내에서 함량의 변화가 가능함은 당연하다.Further, 1.0% by weight of any one or more of the dipeptides of Table 2, 2.0% by weight of glycerin, 2.0% by weight of 1,3-butylene glycol, 1.0% by weight of Fiji-1500, 0.2% by weight of allantoin, 0.2% by weight of DL-panthenol, 3.0 wt% sodium hyaluronate, 15.0 wt% ethanol, 0.2 wt% octyldodeces-16, 0.3 wt% polysorbate-20, 2.0 wt% witch hazel extract, and trace amounts of citric acid, preservatives, flavors, pigments and residuals Ointment may be prepared by mixing purified water. As the content is exemplary, it is obvious that the content can be changed within various ranges.
또한, 상기 표2의 다이펩타이드를 함유하여 스킨, 로션, 크림, 파운데이션, 에센스, 젤, 팩, 폼 클렌징, 비누와 같은 화장료, 또는 피부외용 연고와 같은 약품 연고 형태로 제조할 수 있다.In addition, the dipeptide of Table 2 may be included to prepare a skin, lotion, cream, foundation, essence, cosmetics such as gels, packs, foam cleansing, soap, or a cosmetic ointment such as an external skin ointment.

Claims (4)

  1. SI(세린-이소류신), YK(타이로신-라이신), VC(발린-시스테인), MD(메티오닌-아스파트산), WF(트립토판-페닐알라닌), NR(아스파라진-아르기닌), DP(아스파트산-프로린), YE(타이로신-글루탐산), RM(아르기닌-메티오닌), QT(글루타민-트레오닌), LH(류신-히스티딘), SP(세린-프로린), IT(이소류신-트레오닌), FW(페닐알라닌-트립토판), AP(알라닌-프로린), WP(트립토판-프로린), AN(알라닌-아스파라진), AE(알라닌-글루탐산), DT(아스파트산-트레오닌), PT(프로린-트레오닌), WD(트립토판-아스파트산), NA(아스파라진-알라닌), WY(트립토판-타이로신), AS(알라닌-세린), DG(아스파트산-글라이신), SY(세린-타이로신), NY(아스파라진-타이로신), LE(류신-글루탐산), VH(발린-히스티딘), TI(트레오닌-이소류신), LR(류신-아르기닌), FN(페닐알라닌-아스파라진), YR(타이로신-아르기닌), NE(아스파라진-글루탐산), SL(세린-류신), GL(글라이신-류신), MY(메티오닌-타이로신), AA(알라닌-알라닌), IQ(이소류신-글루타민), HH(히스티딘-히스티딘), NP(아스파라진-프로린), RP(아르기닌-프로린), SD(세린-아스파트산), AK(알라닌-라이신), TD(트레오닌-아스파트산), KY(라이신-타이로신), LF(류신-페닐알라닌), IK(이소류신-라이신), AF(알라닌-페닐알라닌), RS(아르기닌-세린), FK(페닐알라닌-라이신), ST(세린-트레오닌), EP(글루탐산-프로린), WL(트립토판-류신), NC(아스파라진-시스테인), RC(아르기닌-시스테인), SQ(세린-글루타민), WV(트립토판-발린), SM(세린-메티오닌), PA(프로린-알라닌), YA(타이로신-알라닌), HY(히스티딘-타이로신), YD(타이로신-아스파트산), RD(아르기닌-아스파트산), KD(라이신-아스파트산), DD(아스파트산-아스파트산), YI(타이로신-이소류신), AR(알라닌-아르기닌), AC(알라닌-시스테인), YQ(타이로신-글루타민), VF(발린-페닐알라닌), LC(류신-시스테인), KT(라이신-트레오닌), QW(글루타민-트립토판), RK(아르기닌-라이신), NL(아스파라진-류신), GQ(글라이신-글루타민), GI(글라이신-이소류신), HK(히스티딘-라이신), DH(아스파트산-히스티딘), VD(발린-아스파트산), VY(발린-타이로신), MT(메티오닌-트레오닌), QK(글루타민-라이신), TK(트레오닌-라이신), TV(트레오닌-발린), QQ(글루타민-글루타민), WC(트립토판-시스테인), YY(타이로신-타이로신), ET(글루탐산-트레오닌), QF(글루타민-페닐알라닌), RN(아르기닌-아스파라진), TR(트레오닌-아르기닌), AQ(알라닌-글루타민), GD(글라이신-아스파트산), WA(트립토판-알라닌), IH(이소류신-히스티딘), WW(트립토판-트립토판), QN(글루타민-아스파라진), VI(발린-이소류신), AD(알라닌-아스파트산), VN(발린-아스파라진), CW(시스테인-트립토판), EI(글루탐산-이소류신), SN(세린-아스파라진), WN(트립토판-아스파라진), TG(트레오닌-글라이신), SA(세린-알라닌), GA(글라이신-알라닌), PW(프로린-트립토판), PQ(프로린-글루타민), IG(이소류신-글라이신), SH(세린-히스티딘), VR(발린-아르기닌), KM(라이신-메티오닌), VK(발린-라이신), GF(글라이신-페닐알라닌), NV(아스파라진-발린), RG(아르기닌-글라이신), HW(히스티딘-트립토판), VQ(발린-글루타민), CM(시스테인-메티오닌), KC(라이신-시스테인), WQ(트립토판-글루타민), PD(프로린-아스파트산), NQ(아스파라진-글루타민), AY(알라닌-타이로신), GS(글라이신-세린), TW(트레오닌-트립토판), EF(글루탐산-페닐알라닌), EG(글루탐산-글라이신), IV(이소류신-발린), QY(글루타민-타이로신), HL(히스티딘-류신), SK(세린-라이신), ID(이소류신-아스파트산), TS(트레오닌-세린), GW(글라이신-트립토판), PI(프로린-이소류신), NH(아스파라진-히스티딘), PY(프로린-타이로신), TP(트레오닌-프로린), ED(글루탐산-아스파트산), DV(아스파트산-발린), DA(아스파트산-알라닌), NT(아스파라진-트레오닌), DQ(아스파트산-글루타민), PF(프로린-페닐알라닌), SV(세린-발린), DS(아스파트산-세린), GY(글라이신-타이로신), WR(트립토판-아르기닌), NN(아스파라진-아스파라진), FA(페닐알라닌-알라닌), TQ(트레오닌-글루타민), IS(이소류신-세린), VE(발린-글루탐산), FR(페닐알라닌-아르기닌), QR(글루타민-아르기닌), RL(아르기닌-류신), TM(트레오닌-메티오닌), CN(시스테인-아스파라진), FL(페닐알라닌-류신), TE(트레오닌-글루탐산), DI(아스파트산-이소류신), RW(아르기닌-트립토판), RT(아르기닌-트레오닌), MQ(메티오닌-글루타민), VP(발린-프로린), WK(트립토판-라이신), QH(글루타민-히스티딘), SE(세린-글루탐산), AG(알라닌-글라이신), HS(히스티딘-세린), HP(히스티딘-프로린), RE(아르기닌-글루탐산), QS(글루타민-세린), SG(세린-글라이신), AL(알라닌-류신), VA(발린-알라닌), YL(타이로신-류신), YT(타이로신-트레오닌), SR(세린-아르기닌), WS(트립토판-세린), RY(아르기닌-타이로신), FI(페닐알라닌-이소류신), VG(발린-글라이신), LV(류신-발린), WM(트립토판-메티오닌), DW(아스파트산-트립토판), DC(아스파트산-시스테인), FG(페닐알라닌-글라이신), HF(히스티딘-페닐알라닌), PG(프로린-글라이신), CE(시스테인-글루탐산), VV(발린-발린), DN(아스파트산-아스파라진), FH(페닐알라닌-히스티딘), GH(글라이신-히스티딘), MW(메티오닌-트립토판), IP(이소류신-프로린), AI(알라닌-이소류신), ES(글루탐산-세린), EA(글루탐산-알라닌), QV(글루타민-발린), MR(메티오닌-아르기닌), VL(발린-류신), PK(프로린-라이신), DM(아스파트산-메티오닌), GG(글라이신-글라이신), YF(타이로신-페닐알라닌), EE(글루탐산-글루탐산), TF(트레오닌-페닐알라닌), ER(글루탐산-아르기닌), CS(시스테인-세린), IA(이소류신-알라닌), YM(타이로신-메티오닌), IM(이소류신-메티오닌), EV(글루탐산-발린), SS(세린-세린), AH(알라닌-히스티딘), EH(글루탐산-히스티딘), NF(아스파라진-페닐알라닌), EM(글루탐산-메티오닌), HA(히스티딘-알라닌), RR(아르기닌-아르기닌), IY(이소류신-타이로신), SC(세린-시스테인), GK(글라이신-라이신), PS(프로린-세린), EY(글루탐산-타이로신), LK(류신-라이신), CQ(시스테인-글루타민), KV(라이신-발린), WE(트립토판-글루탐산), HG(히스티딘-글라이신), EK(글루탐산-라이신), FF(페닐알라닌-페닐알라닌), FM(페닐알라닌-메티오닌), DK(아스파트산-라이신), LT(류신-트레오닌), FD(페닐알라닌-아스파트산), DF(아스파트산-페닐알라닌), FY(페닐알라닌-타이로신), QD(글루타민-아스파트산), LN(류신-아스파라진), KW(라이신-트립토판), NS(아스파라진-세린), PH(프로린-히스티딘), WG(트립토판-글라이신), EL(글루탐산-류신), EQ(글루탐산-글루타민), LA(류신-알라닌), NG(아스파라진-글라이신), NM(아스파라진-메티오닌), WH(트립토판-히스티딘), DE(아스파트산-글루탐산), DL(아스파트산-류신), AV(알라닌-발린), PN(프로린-아스파라진) 및 PR(프로린-아르기닌) 중에서 선택되는 하나 이상의 다이펩타이드를 유효성분으로 포함하는 것을 특징으로 하는 자외선에 의한 홍반반응 억제 조성물.SI (serine-isoleucine), YK (tyrosine-lysine), VC (valine-cysteine), MD (methionine-aspartic acid), WF (tryptophan-phenylalanine), NR (asparagine-arginine), DP (aspartic acid) Proline), YE (tyrosine-glutamic acid), RM (arginine-methionine), QT (glutamine-threonine), LH (leucine-histidine), SP (serine-proline), IT (isoleucine-threonine), FW (phenylalanine- Tryptophan), AP (alanine-proline), WP (tryptophan-proline), AN (alanine-asparagine), AE (alanine-glutamic acid), DT (aspartic acid-threonine), PT (proline-threonine), WD ( Tryptophan-aspartic acid), NA (asparagine-alanine), WY (tryptophan-tyrosine), AS (alanine-serine), DG (aspartic acid-glycine), SY (serine-tyrosine), NY (asparagine- Tyrosine), LE (leucine-glutamic acid), VH (valine-histidine), TI (threonine-isoleucine), LR (leucine-arginine), FN (phenylalanine-asparagine), YR (tyrosine-arginine), NE (asparagine) -Glu Tamsan), SL (serine-leucine), GL (glycine-leucine), MY (methionine-tyrosine), AA (alanine-alanine), IQ (isoleucine-glutamine), HH (histidine-histidine), NP (asparagine- Proline), RP (arginine-proline), SD (serine-aspartic acid), AK (alanine-lysine), TD (threonine-aspartic acid), KY (lysine-tyrosine), LF (leucine-phenylalanine), IK (Isoleucine-lysine), AF (alanine-phenylalanine), RS (arginine-serine), FK (phenylalanine-lysine), ST (serine-threonine), EP (glutamic acid-proline), WL (tryptophan-leucine), NC ( Asparagine-cysteine), RC (arginine-cysteine), SQ (serine-glutamine), WV (tryptophan-valine), SM (serine-methionine), PA (proline-alanine), YA (tyrosine-alanine), HY ( Histidine-tyrosine), YD (tyrosine-aspartic acid), RD (arginine-aspartic acid), KD (lysine-aspartic acid), DD (aspartic acid-aspartic acid), YI (tyrosine-isoleucine), AR (alanine-arginine), AC (alanine- Stain), YQ (tyrosine-glutamine), VF (valine-phenylalanine), LC (leucine-cysteine), KT (lysine-threonine), QW (glutamine-tryptophan), RK (arginine-lysine), NL (asparagine- Leucine), GQ (glycine-glutamine), GI (glycine-isoleucine), HK (histidine-lysine), DH (aspartic acid-histidine), VD (valine-aspartic acid), VY (valine-tyrosine), MT (Methionine-threonine), QK (glutamine-lysine), TK (threonine-lysine), TV (threonine-valine), QQ (glutamine-glutamine), WC (tryptophan-cysteine), YY (tyrosine-tyrosine), ET ( Glutamic acid-threonine), QF (glutamine-phenylalanine), RN (arginine-asparagine), TR (threonine-arginine), AQ (alanine-glutamine), GD (glycine-aspartic acid), WA (tryptophan-alanine), IH (isoleucine-histidine), WW (tryptophan-tryptophan), QN (glutamine-asparagine), VI (valine-isoleucine), AD (alanine-aspartic acid), VN (valine-asparagine), CW (si Stain-tryptophan), EI (glutamic acid-isoleucine), SN (serine-asparagine), WN (tryptophan-asparagine), TG (threonine-glycine), SA (serine-alanine), GA (glycine-alanine), PW (Proline-tryptophan), PQ (proline-glutamine), IG (isoleucine-glycine), SH (serine-histidine), VR (valine-arginine), KM (lysine-methionine), VK (valine-lysine), GF ( Glycine-phenylalanine), NV (asparagine-valine), RG (arginine-glycine), HW (histidine-tryptophan), VQ (valine-glutamine), CM (cysteine-methionine), KC (lysine-cysteine), WQ ( Tryptophan-glutamine), PD (proline-aspartic acid), NQ (asparagine-glutamine), AY (alanine-tyrosine), GS (glycine-serine), TW (threonine-tryptophan), EF (glutamic acid-phenylalanine), EG (glutamic acid-glycine), IV (isoleucine-valine), QY (glutamine-tyrosine), HL (histidine-leucine), SK (serine-lysine), ID (isoleucine-aspartic acid), TS (threonine-serine) , GW (glycine-tryptophan), PI (proline-isoleucine), NH (asparagine-histidine), PY (proline-tyrosine), TP (threonine-proline), ED (glutamic acid-aspartic acid), DV (aspartic acid) -Valine), DA (aspartic acid-alanine), NT (asparagine-threonine), DQ (aspartic acid-glutamine), PF (proline-phenylalanine), SV (serine-valine), DS (aspartic acid- Serine), GY (glycine-tyrosine), WR (tryptophan-arginine), NN (asparagine-asparagine), FA (phenylalanine-alanine), TQ (threonine-glutamine), IS (isoleucine-serine), VE (valine Glutamic acid), FR (phenylalanine-arginine), QR (glutamine-arginine), RL (arginine-leucine), TM (threonine-methionine), CN (cysteine-asparagine), FL (phenylalanine-leucine), TE (threonine Glutamic acid), DI (aspartic acid-isoleucine), RW (arginine-tryptophan), RT (arginine-threonine), MQ (methionine-glutamine), VP (valine-proline), WK (tryptophan-lysine), QH ( Glue Tamine-histidine), SE (serine-glutamic acid), AG (alanine-glycine), HS (histidine-serine), HP (histidine-proline), RE (arginine-glutamic acid), QS (glutamine-serine), SG (serine Glycine), AL (alanine-leucine), VA (valine-alanine), YL (tyrosine-leucine), YT (tyrosine-threonine), SR (serine-arginine), WS (tryptophan-serine), RY (arginine- Tyrosine), FI (phenylalanine-isoleucine), VG (valine-glycine), LV (leucine-valine), WM (tryptophan-methionine), DW (aspartic acid-tryptophan), DC (aspartic acid-cysteine), FG (Phenylalanine-glycine), HF (histidine-phenylalanine), PG (proline-glycine), CE (cysteine-glutamic acid), VV (valine-valine), DN (aspartic acid-asparagine), FH (phenylalanine-histidine) , GH (glycine-histidine), MW (methionine-tryptophan), IP (isoleucine-proline), AI (alanine-isoleucine), ES (glutamic acid-serine), EA (glutamic acid-alanine), QV (glutamine-valine), MR (methionine-a Guinin), VL (valine-leucine), PK (proline-lysine), DM (aspartic acid-methionine), GG (glycine-glycine), YF (tyrosine-phenylalanine), EE (glutamic acid-glutamic acid), TF (threonine -Phenylalanine), ER (glutamic acid-arginine), CS (cysteine-serine), IA (isoleucine-alanine), YM (tyrosine-methionine), IM (isoleucine-methionine), EV (glutamic acid-valine), SS (serine- Serine), AH (alanine-histidine), EH (glutamic acid-histidine), NF (asparagine-phenylalanine), EM (glutamic acid-methionine), HA (histidine-alanine), RR (arginine-arginine), IY (isoleucine- Tyrosine), SC (serine-cysteine), GK (glycine-lysine), PS (proline-serine), EY (glutamic acid-tyrosine), LK (leucine-lysine), CQ (cysteine-glutamine), KV (lysine-valine ), WE (tryptophan-glutamic acid), HG (histidine-glycine), EK (glutamic acid-lysine), FF (phenylalanine-phenylalanine), FM (phenylalanine-methionine), DK (aspartic acid-lysine), L T (leucine-threonine), FD (phenylalanine-aspartic acid), DF (aspartic acid-phenylalanine), FY (phenylalanine-tyrosine), QD (glutamine-aspartic acid), LN (leucine-aspartazine), KW (Lysine-tryptophan), NS (asparagine-serine), PH (proline-histidine), WG (tryptophan-glycine), EL (glutamic acid-leucine), EQ (glutamic acid-glutamine), LA (leucine-alanine), NG (Asparagine-glycine), NM (asparagine-methionine), WH (tryptophan-histidine), DE (aspartic acid-glutamic acid), DL (aspartic acid-leucine), AV (alanine-valine), PN (proline -Asparagine) and PR (proline-arginine) and at least one dipeptide selected from the erythema reaction inhibiting composition characterized in that it comprises as an active ingredient.
  2. 제1항에 있어서,The method of claim 1,
    상기 조성물 총 중량 중 상기 다이펩타이드를 0.001 ~ 30 중량% 포함하는 것을 특징으로 하는 자외선에 의한 홍반반응 억제 조성물.The erythema suppression composition by ultraviolet rays, characterized in that it comprises 0.001 to 30% by weight of the dipeptide in the total weight of the composition.
  3. 제1항에 있어서,The method of claim 1,
    상기 조성물은 약학적으로 허용 가능한 담체 또는 부형제를 더 포함하는 것을 특징으로 하는 자외선에 의한 홍반반응 억제 조성물.The composition is inhibiting erythema caused by ultraviolet light, characterized in that it further comprises a pharmaceutically acceptable carrier or excipient.
  4. 제1항 내지 제3항 중 어느 한 항에 있어서,The method according to any one of claims 1 to 3,
    상기 조성물은 스킨, 로션, 크림, 파운데이션, 에센스, 젤, 팩, 폼 클렌징, 비누와 같은 화장료, 또는 피부외용 연고와 같은 약품 연고인 것을 특징으로 하는 자외선에 의한 홍반반응 억제 조성물.The composition is a skin, lotion, cream, foundation, essences, gels, packs, foam cleansing, cosmetics such as soap, or a cosmetic ointment, such as an external skin ointment, characterized in that the composition for inhibiting erythema by ultraviolet rays.
PCT/KR2010/001923 2009-03-31 2010-03-30 Composition for inhibiting erythema caused by ultraviolet radiation containing a dipeptide as active ingredient WO2010114275A2 (en)

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KR1020090027344A KR101080271B1 (en) 2009-03-31 2009-03-31 Ultraviolet-induced reaction controlling cosmetic composition containing dipeptide
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KR101080271B1 (en) 2011-11-08

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